A. Joshua Wand, Ph.D

faculty photo
Benjamin Rush Professor of Biochemistry
Department: Biochemistry and Biophysics
Graduate Group Affiliations

Contact information
905 Stellar-Chance Laboratories
Department of Biochemistry & Biophysics
University of Pennsylvania
Philadelphia, PA 19104
Office: (215) 573-7288
Fax: (215) 573-7290
Education:
B.Sc. (Biochemistry (Hons))
Carleton University, 1979.
M.Sc. (Chemistry)
Carleton University, 1981.
Ph.D. (Biophysics)
University of Pennsylvania, 1984.
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Description of Research Expertise

Dr. Wand's research focuses on exploring the relationships between static structure, structural dynamics and function in a range of protein systems. Current efforts are centered on calmodulin, a main player in calcium-mediated signal transduction, a variety of heme-binding proteins, interleukins and their receptors, and ubiquitin. The interaction of calmodulin with several target proteins is being investigated by high resolution multidimensional multinuclear NMR methods with an aim of discovering the full range of interactions displayed by this main player in calcium-mediated signal transduction. A key concept is the balance between changes in structure (enthalpy) and dynamics (entropy) is the binding process. A range of other systems involving protein-protein interactions as well as interactions with small ligands are also being pursued. Through these studies a remarkably rich manifold of fast dynamical modes have been revealed and a surprising functional role for them discovered.

The Wand lab is also committed to continuing improvement and development of novel NMR techniques. They have recently focused on high pressure NMR to probe the protein ensemble, NMR relaxation methods to measure conformational dynamics throughout the protein and a novel method to approach large soluble, unstable and membrane proteins by solution NMR methods. The latter approach involves the use of reverse micelle encapsulation to provide a protective environment for proteins to allow them to be dissolved in low viscosity fluids such as liquid ethane. The initial idea was to use the low viscosity of ethane to overcome the slow tumbling problem for solution NMR spectroscopy presented by large protein in water. Applications have since been expanded to studies of proteins of marginal stability by employing the confined space of the reverse micelle, suppression of protein aggregation to allow study of intermediates of aggregation such as occur in amyloid formation, and studies of membrane proteins.

Selected Publications

Gledhill, J. M., Wand, A. J.: Al NMR: a novel NMR data processing program optimized for sparse sampling. Journal of Biomolecular NMR 52(1): 79-89, 2012.

Fu, Y. N., Kasinath, V., Moorman, V. R., Nucci, N. V., Hilser, V. J., Wand, A. J.: Coupled Motion in Proteins Revealed by Pressure Perturbation. Journal of the American Chemical Society 134(20): 8543-8550, 2012.

Nucci, N. V., Pometun, M. S., Wand, A. J.: Site-resolved measurement of water-protein interactions by solution NMR. Nature Structural & Molecular Biology 18(2): 245-U315, 2011.

Marlow, MS, Dogan, J, Frederick, KK, Valentine, KG, Wand, AJ: The role of conformational entropy in molecular recognition by calmodulin. Nature Chemical Biology 6(5): 352-358, MAY 2010.

Valentine, KG, Peterson, RW, Saad, JS, Summers, MF, Xu, XZ, Ames, JB, Wand, AJ: Reverse Micelle Encapsulation of Membrane-Anchored Proteins for Solution NMR Studies. Structure 18(1): 9-16, JAN 13 2010.

Frederick, KK, Marlow, MS, Valentine, KG, Wand, AJ: Conformational entropy in molecular recognition by proteins. Nature 448(7151): 325-U3, JUL 19 2007.

Igumenova, T.I. , K.K. Frederick, and A.J. Wand : Characterization of the fast dynamics of protein amino acid side chains using NMR relaxation in solution. Chem. Rev 106(5): 1672-1699, 2006.

Babu, CR, Hilser, VJ, Wand, AJ: Direct access to the cooperative substructure of proteins and the protein ensemble via cold denaturation. Nature Structural & Molecular Biology 11(4): 352-357, APR 2004.

Lee, A. L. and Wand, A. J: Microscopic origins of entropy, heat capacity and the glass transition in proteins. Nature 411: 501-504, 2001.

Lee, A. L, Kinnear, S. A. and Wand, A. J: Redistribution and loss of side-chain entropy upon formation of a calmodulinopeptide complex. Nature Struct. Biol 7: 72-77, 2000.

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Last updated: 01/03/2014
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